This application is based on the inhibitory activity of tetrandrine and all of its derivatives, specifically against malaria, as well as the ability of such derivatives, some in particular, to potentiate the effectiveness of antimalarial drugs against multidrug resistant malarial cells in particular. A related application filed concurrently herewith discloses and claims the generic ability of methoxadiantifoline, tetrandrine and certain of its derivatives to potentiate the inhibitory action of primary drugs against multidrug resistant cells generically, and to apparently reverse the normal pump out action of P-glycoprotein in such cells.
A number of diverse drugs have been found effective against malaria. However in many cases, the initial success of physicians in treating this disease is followed by total failure. Drugs which worked initially become totally ineffective after a period of time. An initial period of remission is often followed by a period of frustration during which nothing seems to be effective against the disease. Death becomes inevitable.
Such a phenomenon is often referred to as multidrug resistance. A malarial cell which initially responds to treatment by one or more drugs becomes resistant to treatment by not only the drugs previously used, but but any malarial treatment drug. Martin, Odula and Milhous disclosed the treatment of such multidrug resistance in malaria by using verapamil. xe2x80x9cReversal of Chloroquine Resistance in Plasmodium falciparaum by Verapamil,xe2x80x9d Martin et al, Science, Feb. 28, 1987. Martin et al, reports that Verapamil did reverse chloroquine resistance in malaria cells, but that the verapamil alone had no effect on the malaria. The structural formula of verepamil is shown below: 
The problem with this approach is that verapamil is a calcium channel blocker. While calcium channel blockers are therapeutic in the treatment of hypertension at moderate levels, they are toxic at levels high enough to effect MDR reversal.
Consequently, researchers throughout the world continue to press for techniques for reversing multidrug resistance. A successful clinical technique for reversing multidrug resistance in malaria will be one of the most important breakthroughs in the fight against malaria.
In the present invention, it has been surprisingly found that tetrandrine and its derivatives act to reverse multidrug resistance in malaria and do not show an affinity for calcium channel blocking. Thus the toxicity problems associated with verapamil and its derivatives are avoided.
Perhaps even more surprisingly, it has been found that tetrandrine and its derivatives are also specifically effective against malaria, including multidrug resistant strains, even in the absence of primary treatment drugs. Indeed, the most surprising of all is that the most preferred tetrandrine type structure is actually more effective against multidrug resistant malarial strains than it is against drug sensitive strains.
These surprising and unexpected results, as well as other objects, advantages and features of the present invention will be more fully understood and appreciated by reference to the Description of the Preferred Embodiment and appended drawings.